Obesity prevalence in the US has risen to epidemic proportions. Pharmacotherapy is indicated for weight reduction in patients with body mass index (BMI) >=30 kg/m 2 as well as those with BMI >=27 kg/m 2 in the presence of co-morbid risk factors. However, currently there are very few pharmacologic treatment options for weight reduction, and the available treatments fail to provide adequate benefit for many obese patients because of lack of efficacy, side effects, or contraindications. Hence, there is considerable need for developing new treatments for the management of obesity. Zonisamide, a drug that is currently marketed as an antiepileptic, has been shown to promote significant weight loss in obese patients in a 16-week preliminary investigation conducted by our group. However, the pharmaceutical company that has exclusive marketing rights for zonisamide in the US will not conduct further studies of longer duration with a larger sample of patients to seek a new indication, as the market exclusivity on this drug is due to expire in less than two years. Because Zonisamide can be a potential weapon in our fight against obesity, we wish to pursue this idea further via a randomised clinical trial examining the efficacy of the drug over a year. Since our preliminary trial design did not allow us to assess whether a smaller dose of zonisamide might also be effective, we will examine dose-response in this study in addition to assessment of long-term efficacy and safety. We will also systematically assess whether weight loss achieved with zonisamide treatment can reduce metabolic and cardiovascular risk factors.